Frequent c-fms activation by proviral insertion in mouse myeloblastic leukaemias

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Abstract
Retroviruses lacking oncogenes can induce tumours in animals, and the tumour cells are frequently found to contain proviral DNA inserted next to a proto-oncogene, which is thus placed under the regulatory control of the retroviral long terminal repeat (LTR). This altered regulation leads to overexpression of the proto-oncogene, which presumably contributes to the growth properties of the tumour cells. fim-2 has been described as a retroviral integration site frequently and specifically involved in murine myeloblastic leukaemias induced in vivo or in vitro by the replication-competent Friend murine leukaemia virus (F-MuLV). Here we report that fim-2 spans the 5'-end of the murine proto-oncogene c-fms, known to code for a transmembrane glycoprotein with tyrosine kinase activity probably identical to the receptor of the haemopoietic growth factor, monocyte-macrophage colony-stimulating factor (M-CSF or CSF-1). Proviral integration in the fim-2 region results in a high expression of a normal sized c-fms messenger RNA. We also observe that some tumours have lost the fim-2/c-fms germ line allele. These results provide the first evidence for the presumed involvement of c-fms in myelomonocytic leukaemias.